1. Field of the Invention
The present invention is generally directed to a device and method for measuring, monitoring and recording aqueous outflow from, the eye and relates to a method of delineating the pattern of aqueous outflow and the location and extent of resistance to outflow in glaucoma. Furthermore, the device and method can be utilized to monitor the effect various glaucoma therapies have on the pattern of outflow in glaucoma.
2. Background Art
Glaucoma is a significant public health problem, because glaucoma is a major cause of blindness. The blindness that results from glaucoma involves both central and peripheral vision and has a major impact on an individual's ability to lead an independent life.
Glaucoma is an optic neuropathy (a disorder of the optic nerve) that usually occurs in the setting of an elevated intraocular pressure. The pressure within the eye increases and this is associated with changes in the appearance (“cupping”) and function (“blind spots” in the visual field) of the optic nerve. If the pressure remains high enough for a long enough period of time, total vision loss occurs. High pressure develops in an eye because of an internal fluid imbalance.
The eye is a hollow structure that contains a clear fluid called “aqueous humor.” Aqueous humor is formed in the posterior chamber of the eye by the ciliary body at a rate of about 2.5 microliters per minute. The fluid, which is made at a fairly constant rate, then passes around the lens, through the pupillary opening in the iris and into the anterior chamber of the eye. Once in the anterior chamber, the fluid drains out of the eye through two different routes. In the “uveoscleral” route, the fluid percolates between muscle fibers of the ciliary body. This route accounts for approximately ten percent of the aqueous outflow in humans. The primary pathway for aqueous outflow in humans is through the “canalicular” route that involves the trabecular meshwork and Schlemm's canal.
The trabecular meshwork and Schlemm's canal are located at the junction between the iris and the sclera. This junction or corner is called “the angle.” The trabecular meshwork is a wedge-shaped structure that runs around the circumference of the eye. It is composed of collagen beams arranged in a three-dimensional sieve-like structure. The beams are lined with a monolayer of cells called trabecular cells. The spaces between the collagen beams are filled with an extracellular substance that is produced by the trabecular cells. These cells also produce enzymes that degrade the extracellular material. Schlemm's canal is adjacent to the trabecular meshwork. The outer wall of the trabecular meshwork coincides with the inner wall of Schlemm's canal. Schlemm's canal is a tube-like structure that runs around the circumference of the cornea.
The aqueous fluid travels through the spaces between the trabecular beams, across the inner wall of Schlemm's canal and into the canal. From Schlemm's canal, the fluid flows through a series of about 25 collecting channels that drain into aqueous veins. The aqueous veins, which contain a mixture of aqueous fluid and venous blood, drain into the episcleral venous system. The episcleral venous system forms a plexus of blood vessels on the surface of the eye.
In a normal situation, aqueous production is equal to aqueous outflow and intraocular pressure remains fairly constant in the 15 to 21 mm Hg range. In glaucoma, the resistance through the canalicular outflow system is abnormally high. The increased resistance is believed to be present along the outer aspect of trabecular meshwork and the inner wall of Schlemm's canal. It is believed that the distal outflow system (Schlemm's canal, collecting channels, aqueous veins, episcleral plexus) is normal.
In primary open angle glaucoma, which is the most common form of glaucoma, the abnormal resistance is believed to be along the outer aspect of trabecular meshwork and the inner wall of Schlemm's canal. It is believed that an abnormal metabolism of the trabecular cells leads to an excessive build up of extracellular materials or a build up of abnormally “stiff” materials in this area. Primary open angle glaucoma accounts for approximately eighty-five percent of all glaucoma. Other forms of glaucoma (such as angle closure glaucoma and secondary glaucomas) also involve decreased outflow through the canalicular pathway but the increased resistance is from other causes such as mechanical blockage, inflammatory debris, cellular blockage, etc.
With the increased resistance, the aqueous fluid builds up because it cannot exit fast enough. As the fluid builds up, the intraocular pressure (IOP) within the eye increases. The increased IOP compresses the axons in the optic nerve and also may compromise the vascular supply to the optic nerve. The optic nerve carries vision from the eye to the brain. Some optic nerves seem more susceptible to IOP than other eyes. While research is investigating ways to protect the nerve from an elevated pressure, the only therapeutic approach currently available in glaucoma is to reduce the intraocular pressure.
The clinical treatment of glaucoma is approached in a stepwise fashion. Medication often is the first treatment option. Administered topically or systemically, glaucoma medications work either to reduce aqueous production or to enhance aqueous outflow. When medication fails to adequately reduce the pressure, laser trabeculoplasty often is performed. In laser trabeculoplasty, thermal energy from a laser is applied to a number of noncontiguous spots in the trabecular meshwork. It is believed that the laser energy stimulates the metabolism of the trabecular cells in some way and changes the outflow resistance. If laser trabeculoplasty fails to adequately reduce the pressure, surgery is performed. Currently, all surgical procedures involve the creation of a hole in the sclera that allows aqueous fluid to collect on the surface of the eye.
Newer surgical methods are being developed that target the abnormal area of resistance in the trabecular meshwork. These methods, which include trabeculotomy, goniotomy, goniocurettage, excimer laser trabecular ablation and the GMP BiDirectional Glaucoma shunt (described in WO 00/64393), aim to eliminate the area of resistance and allow aqueous to gain access to the distal outflow system.
The current understanding of the human outflow system is based primarily on histologic study of cadaver eyes and indirect physiological measurements. For instance, the presence and in vitro appearance of the distal outflow system can be demonstrated by injecting tracers (dye, blood, particles) into Schlemm's canal. However, the in vivo behavior of the plexus is unknown. Likewise, the speed of aqueous outflow can be indirectly measured through fluorophotometry. With fluorophotometry, fluorescein dye is applied to the surface of the eye, absorbed into the anterior chamber and then its disappearance from the eye measured with a photometer. However, the pattern and extent of aqueous outflow cannot be measured with this technique.
Some investigators believe that once aqueous humor reaches Schlemm's canal, the fluid travels circumferentially to exit the eye through the collecting channel that offers the least resistance. Others believe that aqueous humor passes quickly through Schlemm's canal and exits the eye through the adjacent collecting channel with minimal circumferential flow. Thus, the pattern of aqueous outflow from a normal eye remains controversial.
Furthermore, some investigators believe that in glaucoma, the resistance through the trabecular meshwork gradually and uniformly increases, until a threshold of resistance is reached after which intraocular pressure increases. Other investigators believe that the abnormal outflow resistance is segmental, affecting only certain areas of the trabecular meshwork. According to this premise, the pattern of segmental resistance would vary among glaucoma patients. Thus, the location and extent of resistance in glaucoma also remains controversial.
Currently, there is no diagnostic tool to analyze the pattern of aqueous outflow or the location of abnormal resistance for an individual patient. Furthermore, there is no diagnostic tool to measure the effect that intervention (medication, laser, surgery) has on aqueous outflow.